Potassium channels make up a diverse group of ion channels that play integral in roles action potential generation and fine-tuning of firing properties of excitable cells. The ether-a-go-gorelated (ERG) potassium channels are a relatively new family of potassium channels. The human ERG ismutant in a form of familial Long QT syndrome or sudden cardiac death. The role of ERG in cells is not fully understood and the identification of mutations in this channel warrant the further examination of the function of this ion channel. The previous funding period for this proposal resulted in the characterization of the Drosophila ERG channel which is mutant in the seizure mutation. The seizure (DERG) channel transcriptional start sites were identified and mapped to three distinct promoters which exhibit cell-specific transcriptional regulation patterns. This proposalexamines the promoters of DERG and their control by specific DNA elements. We propose to examine the seizure (DERG) channel gone by transgenic regulation of promotedreporter gone fusions and identificationof conserved regulatory elements acrossthree Drosophilid species. The coordinate transcriptional regulation of seizure (DERG) and gamma-SNAPwill also be examined. The gamma-SNAP gene lies on the opposite DNA strand and transcribes antiparallel to DERG. The most proximal seizure (DERG) promoter overlaps with the promoter of gamma-SNAP. Interestingly, both genes exhibit the same expression profile on Northern blot analysis. We propose to examine this coordinate regulation by identifying the minimal gamma-SNAP promoter and correlating with the minimal regulatory sequences of the proximal seizure (DERG) promoter. We will also utilize genetic screens to identify genes that modify seizure mutantphenotypes and compdse either accessory subunitsor play similar roles in modulating membrane excitability. In addition, electrophysiological analysisand recombination mapping of the identified mutants will be performed on previously identified seizure (DERG) modifiers. The ease of generating mutations in Drosophila and the availability of the annotated genome allows us to combine physiological analyses with genetics approaches to address questions pertaining ion channel regulation and function. These studies may shed light upon the physiological role of ERG and provide evidence of the pathophysiology of LQT syndrome and epilepsy.